Anna Marie Skalka

faculty photo
Adjunct Professor of Microbiology
Department: Microbiology
Graduate Group Affiliations

Contact information
Fox Chase Cancer Center
333 Cottman Avenue
Philadelphia, PA 19111
Office: 215 728-2490
Fax: 215 728-2778
Education:
B.A. (Biology)
Adelphi University, 1959.
Ph.D. (Microbiology/Biochemistry)
New York University Medical School, 1964.
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Description of Research Expertise

Research Interests
Mechanisms of DNA replication, recombination, and repair. Molecular biology of retroviruses. Epigenetic control of retroviral gene expression.

Key words: DNA integration, DNA repair, retrovirus replication. epigenetic silencing

Description of Research
Our laboratory studies the mechanism and consequences of retroviral DNA integration. Stable integration of viral DNA into the host cell genome is essential for replication of retroviruses and, therefore, an important target for the development of antiviral drugs to treat AIDS. Furthermore, because of the ability to insert their genetic material into a host cell chromosome, retroviruses have potential utility as vectors in gene therapy. The integration process is also a valuable model for other types of DNA rearrangements and transpositions that normally take place in eukaryotic cells and can give rise to cancer. Because host functions are co-opted to facilitate the process, study of retroviral integration provides unique opportunities to uncover critical aspects of cellular biology.

The first two steps in the retroviral DNA integration process are catalyzed by a virus-encoded recombinase, integrase (IN), which splices the ends of viral DNA into host cell genomic DNA. This reaction can be reconstituted in the test tube with the purified protein and model DNA substrates, facilitating analysis of its chemistry. Determination of the three dimensional structures of various subsections of IN proteins has also provided significant insight into function. However, many fundamental questions remain concerning protein organization and mechanistic features of the IN-mediated reactions. To address such questions, we study the IN proteins of the avian sarcoma virus (ASV) and the human immunodeficiency virus type 1 (HIV-1).

In infected cells, IN functions as a component of a large nucleoprotein complex that is formed in the cytoplasm shortly after viral entry. This complex includes newly transcribed viral DNA, other viral proteins, and probably some host proteins. We are especially interested in understanding how this complex gains access to host DNA in the nucleus, and which viral and host proteins participate in the process. We are also interested in understanding the factors that can affect expression of the integrated viral DNA, including its location in the host genome and subsequent epigenetic modifications.

Rotation Projects for 2006-2007
Use of retroviruses to study gene silencing: Use of genetic, biochemical and biophysical methods to study the mechanism of retroviral DNA integration.

Lab personnel:
Richard A. Katz, Ph.D., Staff Scientist, Laboratory Chief
Mark D. Andrake, Ph.D., Staff Scientist
Dineshkumar Dandekar, Postdoctoral Associate
Ravishankar Bojja, Postdoctroral Associate
Andrey Poleshko, Graduate Student, Novosibirsk State University
Natalia Shalginskikh, Graduate Student, Russian State Medical University, Moscow, Russia
George W. Merkel, M.S., Scientific Assistant
Dasha Savage, Student Scientist (Central High School)
Daniel Lipsman, Student Assistant, Central High School, Philadelphia, PA

Selected Publications

Poleshko, A., Palagin, I., Zhang, R., Boimel, P., Castagna, C., Adams, P.D., Skalka, A.M. and katz, R.A.: Identification of cellular proteins that maintain retroviral epigenetic silencing: Evidence for an antiviral response. J. Virol. 85(5): 2313 - 2323, 2008.

Katz, R.A., Jack-Scott, E., Narezkina, A., Palagin, I., Boimel, P., Kulkosky, J., Nicolas, E., Greger, J.G. and Skalka, A.M.: High frequency epigenetic repression and silencing of retroviruses can be antagonized by HDAC inhibitiors and transcriptional activatiors, but uniform reactivation in cell clones is restricted by additional mechanisms. J. Virol. 81(6): 2592 - 2604, 2007.

Ramcharan, J., Colleluori, D.M., Merkel, G., Andrake, M.D. and Skalka, A.M.: Mode of inhibition of HIV-1 integrase by a C-terminal domain-specific monoclonal antibody. Retrovirology 2006.

Daniel, R., Marusich, E., Argyris, E., Zhao, R.Y., Skalka, A.M. and Pomerantz, R.J.: Caffeine inhibits HIV-1 transduction of non-dividing cells. J. Virol. 79(4): 2035 - 2043, 2005.

Katz, R.A., Greger, J.G. and Skalka, A.M.: Effects of cell cycle status on early events in retroviral replication. Journal of Cellular Biochemistry 94: 880-889, 2005.

Ason, B., Knauss, D.J., Balke, A.M., Merkel, G., Skalka, A.M., Reznikoff, W.S.: Targeting Tn5 transposase identifices HIV-1 inhibitors. Antimicrob. Agents Chemother.(49), 2035 - 2043, 2005.

Greger, J.G., Katz, R.A., Ishov, A.M., Maul, G. and Skalka, A.M.: The cellular protein Daxx interacts with Avian Sarcoma Virus integrase and viral DNA to repress viral transcription. J. Virol 79(8): 4610-4618, 2005.

Taganov, K.D., Cuesta, I., Daniel, R., Cirillo, L.A., Katz, R.A., Zaret, K.S. and Skalka, A.M.: Integrase-specific enhancement and suppression of retroviral DNA integration by compacted chromatin structure In Vitro. J. Virol. 78(11): 5848 - 5855, 2004.

Greger, J., Katz, R.A., Taganov, K., Rall, G.F. and Skalka, A.M.: Transduction of terminally differentiated neurons by Avian Sarcoma Virus. J. Virol. 78(9): 4902 - 4906, 2004.

Narezkina, A., Taganov, K.D., Litwin, S., Stoyanova, R., Hayashi, J., Seeger, C., Skalka, A.M. and Katz, R.A.: Genome-wide analyses of avian sarcoma virus integration sites. J. Virol. 78(21): 11656 - 11663, 2004.

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Last updated: 04/23/2013
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